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Lipopolysaccharide increases Na+, K+ -pump, but not ENaC, expression in guinea-pig airway epithelium.
Dodrill-MW; Beezhold-DH; Meighan-T; Kashon-ML; Fedan-JS
Eur J Pharm 2011 Jan; 651(1-3):176-186
Earlier, we found in functional experiments that lipopolysaccharide (LPS; 4 mg/kg; i.p.) hyperpolarized the epithelium by stimulating the transepithelial transport of Na+ in guinea-pig tracheal epithelium. Epithelial sodium channel (ENaC) activity and Na+,K+-pump activity were increased. In this study, we hypothesized that LPS increases the expression of ENaC and the Na+,K+-pump in the epithelium and investigated the levels of transcription and protein abundance. Using qPCR, the effects of LPS on the transcription of alphaENaC, alpha1 Na+,K+-pump, COX-2, eNOS, iNOS, IL-1ß, and TNF-alpha were measured at 3 and 18 h. In the epithelium, LPS increased the transcription of COX-2, IL-1ß, and, to a nonsignificant extent, TNF-alpha at 3 h, but not at 18 h. In alveolar macrophages, TNF-alpha, and, to a nonsignificant extent, COX-2 and IL-1ß were up-regulated at 3 h, but not at 18 h. Even though LPS stimulated the transcription of some genes, alphaENaC and alpha1 Na+,K+-ATPase transcription were not affected. The expressions of alpha-, ß-, and gamma-ENaC and alpha1 Na+,K+-pump from the tracheal epithelium and kidney cortex/medulla were investigated by western blotting. All three ENaC subunits were detected as cleavage fragments, yet LPS had no effect on their expression. LPS increased the expression of the alpha1 subunit and the alpha1, alpha2, and alpha3 subunits, collectively, of the Na+,K+-pump. Taken together, these data indicate that LPS increases Na+ transport downstream of the genetic level, in part, by stimulating the expression of the Na+,K+-pump.
Lung-cells; Lung-function; Animal-studies; Laboratory-animals Endotoxins; Pharmacodynamics; Alveolar-cells; Pulmonary-function; Mucous-membranes; Transport-mechanisms; Genes; Polysaccharides; Cellular-transport-mechanism; Author Keywords: Endotoxin; Lung; Airway epithelium; Epithelial sodium channel (ENaC); Sodium; Potassium ATPase (Na+,K+-ATPase)
Jeffrey S. Fedan, National Institute for Occupational Safety and Health, Health Effects Laboratory Division,1095 Willowdale Road, Morgantown, WV 26505, USA
Issue of Publication
European Journal of Pharmacology